The burdens that exposure to lead and other metal cations places on society and individuals are massive when one considers the amount of money required for health care for those who develop metal cation-induced mental and physical disabilities, and the loss of the productive contributions that these individuals might otherwise make. For example, lead exposure can cause acute or chronic manifestations depending on the amount of lead to which a person has been exposed, and the duration of exposure. Acute exposure to lead most often leads to intestinal colic, while chronic exposure can result in various neurological symptoms, ranging from encephalopathy to psychological deficits, such as decreased intelligence and behavioral disturbances. Other metallic cations, such as mercury and cadmium, can also have adverse effects on nervous, reproductive and immunological systems.
One of the real tragedies in this situation is that, for the most part, this situation is preventable. If convenient, inexpensive, and reliable screening methods existed, they could be applied to identifying individuals at risk and to localizing environmental sources of lead and other metal cations before irreversible health effects occurs.
Most of the methods, such as atomic absorption spectrometry and anodic stripping voltametry, have been directed toward detection of metal cations, including lead, in blood. However, these procedures utilize expensive, specialized equipment that requires highly trained personnel for proper operation, thus making their use in widespread screening programs difficult, if not impossible.
As an alternative, other parameters which might serve as reliable indicators of blood metal cation contamination have been sought. Those which have been identified for lead include an increase in erythrocyte protoporphyrin (S. Piomelle, Low Level Lead Exposure, H. Needleman, editor, Raven Russ, NY, pp. 67-74 (1980)), a decrease in .delta.-aminolevulinic acid dehydratase (ALAD) enzyme activity (S. Hernberg et al., Lancet, I:63-66 (1970)), and a decrease in heme synthetase activity (O. Wada et al., Ind. Health, 10:84-92 (1972)). Of these, only the increase in erythrocyte protoporphyrin (EP) has been exploited for use as a screening method to detect the presence of lead in blood. The major difficulty with this system is that measurement of EP is not sensitive enough for accurate correlation with a blood lead concentration below 25 .mu.g/dl, which is 2.5 times above the limit recently defined by CDC as the "safe" level of lead in blood. (L. Alessio et al., British J. Ind. Med., 38:262-267 (1981).)
ALAD is a zinc-containing enzyme, and inhibition of its enzymatic activity is thought to result from displacement of zinc by metal cations including lead. (E. Jaffe et al., Biol. Trace Element Res., 28:223-232 (1991).) It is generally felt that a decrease in ALAD activity is the first measurable effect of lead contamination and is the most sensitive measure of lead toxicity (Hernberg et al., cited supra.). A decrease in ALAD has been implicated in the pathogenesis of lead poisoning and, thus, may also serve as a reliable indicator of clinical status of a patient exposed to lead or other heavy metals. Astrin et al., Ann Ny Acad. Sci., 514:23 (1987). The difficultly with using this parameter for development of a practical assay for blood lead is that enzyme assays are not generally convenient and rapid enough to use for a widespread screening program.
Thus, there is a need for a reliable and rapid screening and/or diagnostic assay for the presence of lead or other metallic cations in animals and the environment. In addition there is a need for an immunoassay for the quantitative detection of lead and lead-ALAD in blood. There is also a need for a rapid screening assay in a kit to determine metal cation concentrations in fluids derived from humans, animals or the environment.